1. Field of the Invention
The invention relates to the field of methods for determining treatment parameters on a haemofiltration device as well as haemofiltration devices for such methods.
2. Description of the Related Art
Different methods are used in replacement-of-renal-function treatment. In some of these methods, during treatment, blood is continuously taken from a patient and fed into an extracorporeal circulation system where it flows through a blood cleansing element before it is returned to the patient. Most of the time the blood cleansing element comprises a filter element divided into two chambers by means of a semipermeable membrane, with blood flowing through one chamber of said filter element. Presently, above all, filter elements which comprise thousands of hollow fibres are used for this purpose, with blood flowing through the interior of said hollow fibres.
In the case of haemodialysis, a cleansing fluid (dialysis fluid) flows through the other chamber, with said cleansing fluid absorbing by diffusion the substances to be removed from the blood, such as for example urea, and with said cleansing fluid in relation to substances to be left in the blood, such as electrolytes, having a composition similar to that of healthy blood. By means of a component which controls ultrafiltration, volumes of fluid to be eliminated are also removed from the blood chamber to the dialysis fluid chamber of the filter element.
In the case of haemofiltration, in the other chamber of the filter element, hereinafter referred to as the first chamber, there is not a complete flow of a second fluid instead, only ultrafiltrate is fed to this chamber via the membrane, with said ultrafiltrate then being removed via an ultrafiltrate drainage pipe. During this process, the quantity of fluid is far greater than the quantity which would have to be removed for the patient to attain his/her dry weight. In this way a substantial quantity of substances to be removed such as urea, is removed by convection with the ultrafiltrate. At the same time, almost the entire quantity of fluid is replaced by a substitution fluid which is returned to the patient at a suitable position via the extracorporeal circulation system.
Since convection and diffusion can remove molecules of different sizes with different effectiveness through the membrane, a combination of both processes, called haemodiafiltration treatment, is also used. Modern dialysis machines can alternate between these treatment modes without the need for a complex conversion. Some known devices offer the option of providing the dialysis fluid and the substitution fluid on-line during treatment, using water and a respective concentrate. With these devices it is no longer necessary to have enormous quantities of these fluids (up to approx. 200 litres) at the ready in the form of bags. Such a device is e.g. the subject of EP 0 930 080 A1.
So as to be able to monitor the success of replacement-of-renal-function treatment, the determination of treatment parameters with such blood cleansing apparatus, in particular the effectiveness of the blood cleansing element, is of great interest. Effectiveness is usually expressed by stating the clearance of the blood cleansing element.
Clearance K is defined as the blood stream which is completely freed of a substance (e.g. urea) by the blood cleansing element. In the case of haemodialysis treatment it is a prerequisite that when the dialysis fluid enters the dialyser, said dialysis fluid does not contain any of the substance to be removed. Clearance depends on the area and material of the dialyser and the respective operating conditions (the flow of blood, dialysis fluid and ultrafiltration fluid). Clearance can occur both as a result of diffusion and as a result of convection via the membrane of the filter element, the dialyser.
The term clearance can also be widened so as to cover p substances such as e.g. sodium ions which are already present in the dialysis fluid. This is then called dialysance D which is defined as the blood flow which is completely brought to the concentration level in the dialysis fluid.
From clearance K, the non-dimensional quantity Kt/V can be calculated, where t is the treatment duration and V is the distribution volume of the substance in the human body. It is very common to use Kt/V for urea as the measure of the efficiency of dialysis treatment.
However, measuring the urea concentration has been relatively expensive up to now. Either it necessitates the taking of blood specimens, which is disagreeable to patients and moreover does not allow fast automatic evaluation, or it involves measuring the used dialysis fluid which is still rather expensive.
Presently determining the ionic dialysance provides an alternative. The basic principle of such measurements is based on the fact that the diffusion behaviour of urea and small ions such as Na+, Cl, etc. is almost identical. The concentration of these ions in the dialysis fluid can easily be determined by measuring the electrical conductivity which in turn can be determined using measuring cells which are of relatively simple design. Instead of determining the urea clearance, the ion dialysance is thus determined first. Due to the same diffusion behaviour to be expected, the ion dialysance can then be assumed to be identical to the urea clearance.
In the state of the art there are various publications for calculating the dialysance (e.g. J. Sargent and F. Gotch, in: Replacement of Renal Functions by Dialysis, ed. C. Jacobs et al., Kluwer, Dordrecht, Boston, London, 1996, p. 39). Without ultrafiltration, it can be expressed in the so-called dialysate-side form, in the following equation:                               D          =                      Qd            ⁢                                          Cdo                -                Cdi                                                              α                  ⁢                                                                           ⁢                  Cbi                                -                Cdi                                                    ,                            (        1        )            where    Qd: Dialysis flow;    Cdo: Concentration of the investigated substance in the outgoing dialysis fluid;    Cdi: Concentration of the investigated substance in the incoming dialysis fluid;    Cbi: Concentration of the investigated substance in the blood streaming into the extracorporeal circulation system (wherein only the volume fraction is to be considered in which this substance is effectively dissolved); and    α: Gibbs-Donnan factor.
The Gibbs-Donnan factor takes into account that on the blood side, charged ions such as for example Na+ are partly bound to oppositely charged proteins which are proteins not commonly found in dialysers. This effect would bring about a situation where in the diffusive equilibrium (at insignificant flows) a somewhat greater ion concentration would occur in the blood plasma when compared to that of the dialysis fluid, because an electrical field counteracts diffusion. For the case of sodium ions in the blood plasma, a case particularly relevant in practical application, α is approx. 0.95. If such accuracy is not required, this factor can be ignored.
In equation 1, all quantities except for Cbi can be measured easily. To do so it is sufficient to arrange two conductivity measuring cells in the dialysis fluid circulation system, with said cells determining the conductivity at the inlet and outlet of the dialyser. The respective conductivity can easily be converted to the concentration Cdi and Cdo. If the concentration Cdi has also been specified and is thus known, for example because precisely defined fluids are used, then there is no need to measure Cdi. Most of the time the dialysis fluid flow Qd is predetermined by the haemodialysis machine and is thus also known. Otherwise it is of course possible to provide respective sensors in addition.
For practical reasons, measuring the conductivity on the blood side is however problematical. It is however possible, by changing the concentration Cdi, to eliminate the term Cbi. This can for example take place in the form of a concentration step or a bole. The former is described in DE 39 38 662 A1; the latter in DE 197 47 360 A1 or WO 00/02604 A1 (we herewith explicitly refer to these publications). Below, both options are considered as alternatives for a change in the concentration of a fresh fluid which is required for blood treatment. The dialysance can then be determined as follows:                               D          =                                    Qd              ⁡                              (                                  1                  -                                                            Cdo2                      -                      Cdo1                                                              Cdi2                      -                      Cdi1                                                                      )                                      =                          Qd              ⁡                              (                                  1                  -                                                            Δ                      ⁢                                                                                           ⁢                      Cdo                                                              Δ                      ⁢                                                                                           ⁢                      Cdi                                                                      )                                                    ,                            (        2        )            where    Cdi 1,2: Cdi before and after the change (step), or outside and during the change (bole); and    Cdo 1,2: Cdo before and after the change (step), or outside and during the change (bole).
In the case of a stepped change, ΔCbi or ΔCdo represent simple differences; in the case of the bole method, they refer to the change integrated via the bole, relative to a base level.
By means of D, it is now possible to determine Cbi by using equation 1. An equivalent approach would be to first determine Cbi as a parameter to be determined from an equation corresponding to equation 2, which results from equation 1 if D is eliminated
Further methods are known from the state of the art, such as from WO 98/32476 A1 or EP 0 658 352 A1, which methods do not explicitly make use of equation 2 in determining D, but which in the final analysis are always based on the principle of bringing about a change in the physical-chemical characteristic Cdi, and of holding on to the respective change Cdo in order to permit a statement about the physical-chemical characteristic Cbi on the blood side, or about the filter efficiency D.
Without exception, the state of the art mentions methods which make possible a determination during haemodialysis treatment. There are—at times differing—details as to how the ultrafiltration flow Qf, removed from the blood during haemodialysis treatment, can be taken account of in equations (1) and (2). This is for example the case in EP 1 062 960 A2, wherein Qd is substituted by the sum of the flows Qd and Qf. However, in the case of haemodialysis treatment, the ultrafiltration flow Qf is very small when compared to the dialysis fluid flow Qd and the blood flow Qb, in other words, the interference effect is relatively minor. Typical values for Qf=15 ml/min; for Qd=500 ml/min; and for Qb=300 ml/min.
However, in the case of replacement-of-renal-function treatment, knowledge of the efficiency of the blood cleansing element is of just as much interest in the case of haemofiltration treatment, either on its own or in combination with haemodialysis treatment in the form or haemodiafiltration treatment.
In this connection it is at first not obvious as to how the concept of ion dialysance can be transferred to this case. In haemofiltration there is no dialyser through which a dialysis fluid flows. Moreover, both in haemofiltration and in haemodiafiltration, large quantities of fluid are removed via a haemofilter or haemodialyser and at the same time are added in another location to the extracorporeal blood circulation system. Flows of up to 100 ml/min are achieved which can no longer be considered as being very small when compared to the flow of dialysis fluid (in haemodiafiltration) and when compared to the blood flow.